Enhancer dynamics during mammalian evolution and differentiation
One of the most fundamental and fascinating questions in biology is how different types of cells in a human body are derived from the same genome but possess distinct appearances and functions. Temporal and spatial- specific gene transcription, which is tightly controlled by cis-regulatory elements such as promoters and enhancers, has been regarded as one of the main contributor. In this seminar, I will first talk about recent effort by the mouse ENCODE consortium, in which we produced and analyzed more than 1,000 coordinated data sets, including transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains, in over 100 mouse cell types and tissues. By comparing the data from human ENCODE project, we found that although the majority of gene expression patterns and cis-regulatory elements are conserved between the two species, a large degree of gene regulatory elements appear to be species-specific and these species-specific elements are enriched for genes in certain pathways, such as immune system and metabolic process, suggesting that different sets of genes evolve at distinct rates. In the second part of my talk, I will illustrate how epigenetic priming of enhancers signifies developmental competence. In this project, we generated the transcriptome and enhancer landscape in five developmental stages during pancreatic differentiation of human ES cells, including hESCs, definitive endoderm (DE), primitive gut tube (GT), posterior forgut (FG), and pancreatic endoderm (PE). We observed that acquisition of a poised chromatin state at enhancers is a general mechanism by which progenitor cells gain the competence to rapidly activate lineage- specific genes in response to inductive signals.